The present invention relates to the processing and analyzing of endocardiac acceleration signals for use in the diagnosis of a patient condition and the control of an active medical device, and more particularly for the evaluation of the effectiveness, and the search for optimal configuration, of an active medical device implementing a technique known as CRT (Cardiac Resynchronization Therapy) or BVP (Bi-Ventricular Pacing).
In the particular case of CRT devices, an apparatus is implanted within a patient that is provided with electrodes that allow for stimulating the ventricles. The device is able to monitor the cardiac rhythm and to deliver, if necessary, electric impulses to stimulate the left ventricle and right ventricle in order to resynchronize them. For this purpose, the device applies between the two ventricular stimulations a variable intra-ventricular delay, which may be positive or negative, and is adjusted so as to resynchronize the contraction of the ventricles with fine optimization of the hemodynamic state of the patient. One such CRT device is described, for example, in EP 1 108 446 A1 and its corresponding U.S. Patent Publication U.S. Pat. No. 6,556,866 (ELA Medical).
It is essential, in the implementation of such a therapy in patients suffering from cardiac insufficiency or failure, to evaluate the effectiveness of the therapy in order to appreciate the relevance of it, and in the affirmative to maintain its effectiveness by modifying as needed the operation parameters of the implanted device.
The specific parameters of the CRT stimulation are generally represented by a “stimulation configuration”, which is a combination of the characteristics relative to the “stimulation sites” and of the characteristics relative to the “stimulation sequence”. The “stimulation sites” refer to the physical location of the intracardiac electrodes in relation to myocardium tissue. These sites can be selected at the time of the implantation by a suitable positioning of the electrodes. In the case of the prostheses known as “multisite” where the device comprises several electrodes placed in the same cardiac cavity, the modification of the stimulation site in this one cavity is also possible by an internal commutation of the device that selects one or more electrodes positioned at different locations on the myocardium. The concept of “stimulation sequence” refers on the one hand to the order in which the stimulation impulses are applied to the heart (e.g., atrium/left ventricle/right ventricle), and on the other hand to the time intervals separating the application of these successive impulses. Here still, the stimulation sequence is parameterized at implantation time, but can be modified thereafter by selecting the internal commutations of the device and by adjustment of the sequencing parameters of the stimulation impulses.
It is necessary to regularly evaluate the relevance of the stimulation configuration, because it conditions the effectiveness of the therapy with bi-ventricular pacing. Moreover, the beneficial effects provided by this therapy can result, in the long term, in revaluing the initial configuration for modifying eventually the choice of the sites and/or the pacing sequence parameters.
One of the known practices used to optimize the pacing parameters concerns estimating the characteristic delays of the systole, in particular the time of opening of the aortic valve, by an echographic evaluation. This procedure, which must be implemented in hospital by qualified personnel, is long and expensive and cannot be applied as often as it would be useful or necessary, without interfering with the daily life of the patient.
Another solution, suggested by the above mentioned EP 0 108 446 A1, concerns evaluating the degree of synchronization of the contractions of the ventricles by a measurement of intracardiac bio-impedance, this data being indeed representative of the cardiac flow and thus of the fraction of ejection, considered as a reference hemodynamic parameter.
The present invention is based on another approach to bi-ventricular stimulation, namely implementing an analysis of endocardiac acceleration (indicated hereafter as “EA”). Indeed, the clinical studies that were undertaken indicate that endocardiac acceleration is a parameter that makes it possible to provide very complete information about the functional state of the myocardium, as well in the case of a normal function and a defective operation: the endocardiac acceleration, which is measured by an accelerometer directly in contact with the cardiac muscle (generally, but not exclusively, with the ventricular right apex, sometimes with the right atrium), reflects indeed very precisely and in real-time the phenomena contributing to the mechanical functioning of the heart.
More precisely, the publication EP 0 515 319 A1 and its corresponding U.S. Pat. No. 5,304,208 (Sorin Biomedica Cardio SpA) teaches the method of collecting an endocardiac signal of acceleration by means of an endocavitary probe equipped with a pacing distal electrode implanted in the lower part of the ventricle and integrating a microaccelerometer that allows measuring an endocardiac acceleration. The endocardiac signal of acceleration collected (i.e., detected) during a cardiac cycle forms two principal components, corresponding to the two major sounds of the heart (S1 and S2 sounds of the phonocardiogram) which is possible to recognize in each cardiac cycle:                the first component of endocardiac acceleration (“EA1”), whose variations of amplitude are closely related to the variations of the pressure in the ventricle (the maximum peak-to-peak of this component EA1, called PEA1 amplitude, being more precisely correlated to the positive maximum of the variation of pressure dP/dt in the left ventricle) and can thus constitute a parameter representative of the contractility of the myocardium, itself related to the level of activity of the sympathetic nerve system; and        the second endocardiac component of acceleration (“EA2”) which occurs during the phase of isovolumic ventricular relaxation. This second component is produced, mainly, by the closing of the aortic and pulmonary valves.        
The detected signal EA also may contain one or two other components, called EA3 and EA4, corresponding to the S3 and S4 sounds of the phonocardiogram. These sounds generally are the sign of a cardiac failure (EA3 being a priori due to the vibrations of the myocardium walls during a fast filling condition, and EA4 being due to the atrial contraction). The term “EAx component” will refer hereafter indifferently to one of the four EAx components, preferably, but not limited to, component EA1 or component EA2.
The EP 0 655 260 A1 and its counterpart U.S. Pat. No. 5,496,351 (Sorin Biomedica Cardio SpA) describes a manner of processing the signal of endocavitary acceleration delivered by the sensor located at the extremity of the probe and the method to derive from it two values related to the respective peaks of endocardiac acceleration. These values are useful in particular for the detection of cardiac disorders and the application or not of a defibrillation therapy.
The EP 1 736 203 A1 and its counterpart U.S. Patent Application Publication U.S. 20060293715 (ELA Medical) describes an application specific to bi-ventricular pacing implants, concerning using the parameters related to endocardiac acceleration to determine an optimal pacing configuration for the patient, at the time of the implantation or subsequently. Various measurements are taken to characterize the EA signal, and are combined to give a composite index of performance. The choice of the final pacing configuration is then one that which maximizes the index of performance.
U.S. Pat. No. 7,139,609 B1 refers to an implanted device that provides a follow-up of the cardiac function starting from an endocardiac acceleration signal, to optimize the general operation of a pacemaker or to apply a ventricular resynchronization therapy. Each cardiac cycle is analyzed to identify the two major sounds and to analyze the signal in order to deduct some from the parameters such as dP/dt, ejection volume, etc.
The EP 1 741 387 A1 refers to a diagnosis technique of measuring the peak-to-peak amplitude of EA1 (called PEA1) and/or the peak-to-peak amplitude of EA2 (called PEA2) during several successive cycles, and from this to analyze the variations of the detected amplitude to detect a situation of apnea or of hypopnea, and to deliver a suitable alarm.
It will be noted that although the present description refers mainly to the analysis of a signal EA delivered by an implanted sensor (typically, a sensor placed on a endocavitary probe), the invention is equally applicable to an analysis that is carried out using an external signal EA obtained in a noninvasive manner. Such an external signal EA can result, for example, from a sensor fixed on the chest of the patient at the level of the sternum, the ECG signal being simultaneously collected by means of external electrodes and being recorded. Thus, it should be understood that the term “signal EA” means and includes either an external signal EA, obtained noninvasively, or an endocavitary signal EA, obtained by an acceleration sensor mounted on a probe implanted in direct contact with the myocardium of the patient. In the latter case, the implanted device also typically will acquire an electrogram signal EMG that is simultaneously recorded with the endocavitary signal EA.